Coronary artery disease is the first cause of death worldwide, and as a complex
disease implies the interplay between genetic and environmental factors. Common
genetic variants explain only 15-20% of its heritability. DNA methylation, which
regulates the gene expression without altering the DNA sequence, has been proposed as
a heritable signature to explain this missing heritability and as a mediator effect of
lifestyle and environment on health.
To study the relationship between DNA methylation ...

Coronary artery disease is the first cause of death worldwide, and as a complex
disease implies the interplay between genetic and environmental factors. Common
genetic variants explain only 15-20% of its heritability. DNA methylation, which
regulates the gene expression without altering the DNA sequence, has been proposed as
a heritable signature to explain this missing heritability and as a mediator effect of
lifestyle and environment on health.
To study the relationship between DNA methylation and smoking, air pollution,
and cardiovascular risk factors (obesity, lipid profile, and HDL functionality) we used
epigenome-wide association studies, Mendelian randomization, and multi-stage omics
integration approaches. We included data from ten studies, but the results were mainly
based on the REGICOR (REgistre GIroní del COR) cohort.
We report the association between smoking and 63 methylation sites (CpGs). We
did not find association between air pollution and DNA methylation. We identified 94
CpGs associated with obesity and 14 with lipid profile. We observed that methylation at
CPT1A and SLC7A11 can modify or be affected by the triglycerides levels, highlighting
the complexity of the lipids homeostasis. Finally, we performed the first study showing
an association between DNA methylation and HDL functionality.
As conclusions of this research, smoking is strongly associated with a distinctive
methylation pattern and there is a relationship between DNA methylation and several
cardiovascular risk factors, although its causality is complex.